One of our major projects is a laboratory-session-based interventional study of heavy social drinkers, with real-world outcome measures. We are harnessing a property of memory called reconsolidation, whereby recently activated memories become briefly vulnerable to disruption. The memories in this instance are the Pavlovian associations that link alcohol-related cues to the responses of craving and drinking. In a procedure called retrieval-extinction, we reactivate those associations through actual intoxication (using each participants favorite drink); then we disrupt them with repeated exposure to personalized drinking-related stimuli. Data from other investigators, in smokers and heroin users, have shown that this procedure can lead to a remarkably generalizable unlinking of cues from craving even after people leave the laboratory setting and return to their usual environments. We are testing that with the smartphone-based daily assessments that have become our units specialty. The protocol is ongoing. Another major project is to develop Just-in-Time Adaptive Interventions (JITAIs) for treatment of substance-use disorders. This is the next major outgrowth of our work with ambulatory assessment of heroin and cocaine usersan ambulatory treatment via smartphone app. The first goal is to hone content of the intervention. We are preparing to do that with perhaps the most purely psychotherapeutic protocol ever conducted at the NIDA IRP, using both cognitive-behavioral therapy and a mindfulness-based approach called ACT (Acceptance and Commitment Therapy). Our use of these psychotherapies comes with two innovations, one technological (delivery mostly via text on smartphones) and the other methodological (delivery is microrandomized, such that we can test which approach is most immediately helpful under which circumstances in daily life). The protocol is SRC-approved and IRB-approved, and we are finalizing the materials for it. We will start with a formative-research phase in which we interview opioid and cocaine users about their preferences for a mobile-treatment app. This will lead to a clinical trial, which will ultimately incorporate the predictive analytics being developed here by our staff, so that momentary interventions can be pushed when and where the patient needs them. A third project is a translational human study that we developed in collaboration with preclinical investigators at the NIDA IRP and extramural addiction researchers. It derives from NIDA IRP work with orbitofrontal mechanisms of decision-making in rats, and from adaptation of that work for healthy human volunteers in neuroimaging studies by extramural scientists. Here, the methods and outcome measures will be entirely behavioral. We want to assess whether people with opioid-use disorder are detectably impaired in a type of low-level associative learning called outcome inferencing, and whether that impairment is associated with their patterns of opioid use. There is no treatment component in the protocol itself, but the knowledge gained will inform our future treatment studies. Approval of this protocol is under way.